Mechanical Ventilation Redistributes Blood to Poorly Ventilated Areas in Experimental Lung Injury Objectives: Determine the intra-tidal regional gas and blood volume distributions at different levels of atelectasis in experimental lung injury. Test the hypotheses that pulmonary aeration and blood volume matching is reduced during inspiration in the setting of minimal tidal recruitment/derecruitment and that this mismatching is an important determinant of hypoxemia. Design: Preclinical study. Setting: Research laboratory. Subjects: Seven anesthetized pigs 28.7 kg (SD, 2.1 kg). Interventions: All animals received a saline-lavage surfactant depletion lung injury model. Positive end-expiratory pressure was varied between 0 and 20 cm H2O to induce different levels of atelectasis. Measurements and Main Results: Dynamic dual-energy CT images of a juxtadiaphragmatic slice were obtained, gas and blood volume fractions within three gravitational regions calculated and normalized to lung tissue mass (normalized gas volume and normalized blood volume, respectively). Ventilatory conditions were grouped based upon the fractional atelectatic mass in expiration (< 20%, 20–40%, and ≥ 40%). Tidal recruitment/derecruitment with fractional atelectatic mass in expiration greater than or equal to 40% was less than 7% of lung mass. In this group, inspiration-related increase in normalized gas volume was greater in the nondependent (818 µL/g [95% CI, 729–908 µL/g]) than the dependent region (149 µL/g [120–178 µL/g]). Normalized blood volume decreased in inspiration in the nondependent region (29 µL/g [12–46 µL/g]) and increased in the dependent region (39 µL/g [30–48 µL/g]). Inspiration-related changes in normalized gas volume and normalized blood volume were negatively correlated in fractional atelectatic mass in expiration greater than or equal to 40% and 20–40% groups (r2 = 0.56 and 0.40), but not in fractional atelectatic mass in expiration less than 20% group (r2 = 0.01). Both the increase in normalized blood volume in the dependent region and fractional atelectatic mass in expiration negatively correlated with PaO2/FIO2 ratio (ρ = –0.77 and –0.93, respectively). Conclusions: In experimental atelectasis with minimal tidal recruitment/derecruitment, mechanical inspiratory breaths redistributed blood volume away from well-ventilated areas, worsening PaO2/FIO2. This work was undertaken at the Hedenstierna Laboratory, Uppsala University, Uppsala, Sweden. Prof. Farmery and Dr. Formenti generated the hypothesis. Drs. Cronin, Camporota, and Formenti designed the experiments. Drs. Cronin, Crockett, and Formenti performed the experiments. Dr. Cronin analyzed the data. Dr. Cronin, Professors Larsson and Hedenstierna, and Drs. Camporota and Formenti interpreted the data. Professors Farmery, Hedenstierna, Larsson, and Dr. Formenti contributed to financial support. All authors critically revised the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Prof. Farmery received support for article research from Wellcome Trust (HMRXGK00). Prof. Larsson’s institution received funding from the Swedish Heart and Lung Foundation. Dr. Formenti was supported by the Medical Research Council (MC_PC_17164), the Oxford University Medical Research Fund (MRF/LSV2014/2091), King’s College London (Challenge Award), and The Physiological Society (Formenti 2018), and he received support for article research from Research Councils UK and Wellcome Trust. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Dr. Federico Formenti, PhD, DPhil, Centre for Human and Applied Physiological Sciences, Faculty of Life Sciences and Medicine, Shepherd’s House, Guy’s Campus, Kings College London, London, SE1 1UL, United Kingdom. E-mail: federico.formenti@outlook.com This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Targeted Temperature Management at 33 Versus 36 Degrees: A Retrospective Cohort Study Objectives: To determine the association between targeted temperature management goal temperature of 33°C versus 36°C and neurologic outcome after out-of-hospital cardiac arrest. Design: This was a retrospective, before-and-after, cohort study. Setting: Urban, academic, level 1 trauma center from 2010 to 2017. Patients: Adults with nontraumatic out-of-hospital cardiac arrest who received targeted temperature management. Interventions: Our primary exposure was targeted temperature management goal temperature, which was changed from 33°C to 36°C in April of 2014 at the study hospital. Primary outcome was neurologically intact survival to discharge. Secondary outcomes included hospital mortality and care processes. Measurements and Main Results: Of 782 out-of-hospital cardiac arrest patients transported to the study hospital, 453 (58%) received targeted temperature management. Of these, 258 (57%) were treated during the 33°C period (targeted temperature management 33°C) and 195 (43%) were treated during the 36°C period (targeted temperature management 36°C). Patients treated during targeted temperature management 33°C were older (57 vs 52 yr; p < 0.05) and had more arrests of cardiac etiology (45% vs 35%; p < 0.05), but otherwise had similar baseline characteristics, including initial cardiac rhythm. A total of 40% of patients treated during targeted temperature management 33°C survived with favorable neurologic outcome, compared with 30% in the targeted temperature management 36°C group (p < 0.05). After adjustment for demographic and cardiac arrest characteristics, targeted temperature management 33°C was associated with increased odds of neurologically intact survival to discharge (odds ratio, 1.79; 95% CI, 1.09–2.94). Targeted temperature management 33°C was not associated with significantly improved hospital mortality. Targeted temperature management was implemented faster (1.9 vs 3.5 hr from 911 call; p < 0.001) and more frequently in the emergency department during the targeted temperature management 33°C period (87% vs 55%; p < 0.001). Conclusions: Comatose, adult out-of-hospital cardiac arrest patients treated during the targeted temperature management 33°C period had higher odds of neurologically intact survival to hospital discharge compared with those treated during the targeted temperature management 36°C period. There was no significant difference in hospital mortality. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Johnson’s institution received funding from National Institutes of Health (U01HL123008-02) and Medic One Foundation. Dr. Maynard disclosed government work. Dr. Sayre’s institution received funding from Stryker/Physio-Control. Drs. Johnson and Counts receive funding from the Medic One Foundation for unrelated work. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: nickj45@uw.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

The Epidemiology of Sepsis in Chinese ICUs: A National Cross-Sectional Survey Objectives: We performed a national cross-sectional survey to determine the epidemiologic characteristics of patients with sepsis in ICU in China. Design: A cross-section survey study. Setting: Forty-four hospitals in mainland China from December 1, 2015, to January 31, 2016. Patients: All septic patients diagnosed according sepsis-1 criteria admitted to participating ICU. Interventions: None. Measurements and Main Results: We recorded demographic, physiologic, and microbiological data with follow-up for 90 days or death, if sooner. The frequency of sepsis and 90-day mortality rate were computed, and the relationship with gross domestic product determined. Multivariate logistic regression analysis was used to determine risk factors for 90-day mortality in patients with sepsis. Two-thousand three-hundred twenty-two patients with sepsis were included in the analysis, of whom 786 patients (33.9%) had hospital-acquired sepsis. The most common infection site was the lung (68.2%), followed by abdomen (26.6%) and bloodstream (7.8%). The frequency of sepsis in the ICU was 20.6 cases per 100 ICU admissions (95% CI, 15.8–25.4) with a 90-day mortality of 35.5%. The proportion of sepsis, severe sepsis, and septic shock were 3.10%, 43.6%, and 53.3% with a 90-day mortality of 2.78%, 17.69%, and 51.94%, respectively. Older age, low body weight, higher Sequential Organ Failure Assessment score, the number of systemic inflammatory response syndrome criteria, comorbid with heart failure, hematologic cancer, immunosuppression, higher level of lactate, infection site (pneumonia and bloodstream) were associated with 90-day mortality. Conclusions: Sepsis affects a fifth of patients admitted to ICUs in mainland China with a 90-day mortality rate of 35.5%. Our findings indicate that a large burden of sepsis, and we need to focus on sepsis as a quality improvement target in China given the high mortality. In addition, further studies are needed to delineate the epidemiology of sepsis outside the ICU. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by grant from the Development Center for Medical Science and Technology National Health and Family Planning Commission of the People’s Republic of China (WH2015-01-01), a grant from Jiangsu Provincial Key Medical Discipline (ZDXKA2016025) and a grant from Jiangsu Provincial Medical Talent (ZDRCA2016082) and a grant from the Key Research and Development Plan of Jiangsu Province (BE2018743). The authors have disclosed that they do not have any potential conflicts of interest. Trial Registration: ClinicalTrials.gov NCT02448472. For information regarding this article, E-mail: yiyiyang2004@163.com Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Correction and Control of Hyperammonemia in Acute Liver Failure: The Impact of Continuous Renal Replacement Timing, Intensity, and Duration Objectives: Hyperammonemia is a key contributing factor for cerebral edema in acute liver failure. Continuous renal replacement therapy may help reduce ammonia levels. However, the optimal timing, mode, intensity, and duration of continuous renal replacement therapy in this setting are unknown. We aimed to study continuous renal replacement therapy use in acute liver failure patients and to assess its impact on hyperammonemia. Design: Retrospective observational study. Setting: ICU within a specialized liver transplant hospital. Patients: Fifty-four patients with acute liver failure. Interventions: Data were obtained from medical records and analyzed for patient characteristics, continuous renal replacement therapy use, ammonia dynamics, and outcomes. Main Results: Forty-five patients (83%) had high grade encephalopathy. Median time to continuous renal replacement therapy commencement was 4 hours (interquartile range, 2–4.5) with 35 (78%) treated with continuous venovenous hemodiafiltration and 10 (22%) with continuous venovenous hemofiltration. Median hourly effluent flow rate was 43 mL/kg (interquartile range, 37–62). The median ammonia concentration decreased every day during treatment from 151 µmol/L (interquartile range, 110–204) to 107 µmol/L (interquartile range, 84–133) on day 2, 75 µmol/L (interquartile range, 63–95) on day 3, and 52 µmol/L (interquartile range, 42–70) (p < 0.0001) on day 5. The number of patients with an ammonia level greater than 150 µmol/L decreased on the same days from 26, to nine, then two, and finally none. Reductions in ammonia levels correlated best with the cumulative duration of therapy hours (p = 0.03), rather than hourly treatment intensity. Conclusions: Continuous renal replacement therapy is associated with reduced ammonia concentrations in acute liver failure patients. This effect is related to greater cumulative dose. These findings suggest that continuous renal replacement therapy initiated early and continued or longer may represent a useful approach to hyperammonemia control in acute liver failure patients. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Warrillow is a paid employee of Epworth HealthCare, the University of Melbourne (tutorials), and AVANT Insurance (reviewer). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: stephen.warrillow@austin.org.au Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Time to Recognition of Sepsis in the Emergency Department Using Electronic Health Record Data: A Comparative Analysis of Systemic Inflammatory Response Syndrome, Sequential Organ Failure Assessment, and Quick Sequential Organ Failure Assessment Objectives: Early identification of sepsis is critical to improving patient outcomes. Impact of the new sepsis definition (Sepsis-3) on timing of recognition in the emergency department has not been evaluated. Our study objective was to compare time to meeting systemic inflammatory response syndrome (Sepsis-2) criteria, Sequential Organ Failure Assessment (Sepsis-3) criteria, and quick Sequential Organ Failure Assessment criteria using electronic health record data. Design: Retrospective, observational study. Setting: The emergency department at the University of California, San Francisco. Patients: Emergency department encounters between June 2012 and December 2016 for patients greater than or equal to 18 years old with blood cultures ordered, IV antibiotic receipt, and identification with sepsis via systemic inflammatory response syndrome or Sequential Organ Failure Assessment within 72 hours of emergency department presentation. Interventions: None. Measurements and Main Results: We analyzed timestamped electronic health record data from 16,612 encounters identified as sepsis by greater than or equal to 2 systemic inflammatory response syndrome criteria or a Sequential Organ Failure Assessment score greater than or equal to 2. The primary outcome was time from emergency department presentation to meeting greater than or equal to 2 systemic inflammatory response syndrome criteria, Sequential Organ Failure Assessment greater than or equal to 2, and/or greater than or equal to 2 quick Sequential Organ Failure Assessment criteria. There were 9,087 patients (54.7%) that met systemic inflammatory response syndrome-first a median of 26 minutes post-emergency department presentation (interquartile range, 0–109 min), with 83.1% meeting Sequential Organ Failure Assessment criteria a median of 118 minutes later (interquartile range, 44–401 min). There were 7,037 patients (42.3%) that met Sequential Organ Failure Assessment-first, a median of 113 minutes post-emergency department presentation (interquartile range, 60–251 min). Quick Sequential Organ Failure Assessment was met in 46.4% of patients a median of 351 minutes post-emergency department presentation (interquartile range, 67–1,165 min). Adjusted odds of in-hospital mortality were 39% greater in patients who met systemic inflammatory response syndrome-first compared with those who met Sequential Organ Failure Assessment-first (odds ratio, 1.39; 95% CI, 1.20–1.61). Conclusions: Systemic inflammatory response syndrome and Sequential Organ Failure Assessment initially identified distinct populations. Using systemic inflammatory response syndrome resulted in earlier electronic health record sepsis identification in greater than 50% of patients. Using Sequential Organ Failure Assessment alone may delay identification. Using systemic inflammatory response syndrome alone may lead to missed sepsis presenting as acute organ dysfunction. Thus, a combination of inflammatory (systemic inflammatory response syndrome) and organ dysfunction (Sequential Organ Failure Assessment) criteria may enhance timely electronic health record-based sepsis identification. The contents are solely the responsibility of the authors and do not necessarily represent the official views of University of California San Francisco or the National Institutes of Health. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Prasad’s institution received funding from National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through University of California San Francisco (UCSF)-Clinical & Translational Science Institute (CTSI) grant number #A127552, and she received funding as an epidemiologist for EpiExcellence, LLC (consultant). Drs. Prasad, Fang, Abe-Jones, Matthay, and Kangelaris received support for article research from the NIH. Dr. Fang’s institution received funding from the National Heart, Lung, and Blood Institute (NHLBI) K24HL141354 and Patient-Centered Outcomes Research Institute. Dr. Abe-Jones disclosed that data acquisition for this publication was supported by UCSF Academic Research Systems and by the National Center for Advancing Translational Sciences, NIH, through UCSF-CTSI Grant Number UL1 TR001872. Dr. Calfee’s institution received funding from the NHLBI HL140026, GlaxoSmithKline, and Bayer, and she received funding from Bayer, CSL Behring, Prometic, Roche/Genentech, and Quark Pharmaceuticals. Dr. Matthay’s institution received funding from the NIH/NHLBI, GlaxoSmithKline, Bayer, and a Department of Defense grant. Dr. Kangelaris’s institution received funding from NHLBI 1K23HL116800. For information regarding this article, E-mail: Priya.Prasad@ucsf.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Brain Hypoxia Secondary to Diffusion Limitation in Hypoxic Ischemic Brain Injury Postcardiac Arrest Objectives: We sought to characterize 1) the difference in the diffusion gradient of cellular oxygen delivery and 2) the presence of diffusion limitation physiology in hypoxic-ischemic brain injury patients with brain hypoxia, as defined by parenchymal brain tissue oxygen tension less than 20 mm Hg versus normoxia (brain tissue oxygen tension > 20 mm Hg). Design: Post hoc subanalysis of a prospective study in hypoxic-ischemic brain injury patients dichotomized into those with brain hypoxia versus normoxia. Setting: Quaternary ICU. Patients: Fourteen adult hypoxic-ischemic brain injury patients after cardiac arrest. Interventions: Patients underwent monitoring with brain oxygen tension, intracranial pressure, cerebral perfusion pressure, mean arterial pressure, and jugular venous bulb oxygen saturation. Data were recorded in real time at 300Hz into the ICM+ monitoring software (Cambridge University Enterprises, Cambridge, United Kingdom). Simultaneous arterial and jugular venous bulb blood gas samples were recorded prospectively. Measurements and Main Results: Both the normoxia and hypoxia groups consisted of seven patients. In the normoxia group, the mean brain tissue oxygen tension, jugular venous bulb oxygen tension, and cerebral perfusion pressure were 29 mm Hg (SD, 9), 45 mm Hg (SD, 9), and 80 mm Hg (SD, 7), respectively. In the hypoxia group, the mean brain tissue oxygen tension, jugular venous bulb oxygen to brain tissue oxygen tension gradient, and cerebral perfusion pressure were 14 mm Hg (SD, 4), 53 mm Hg (SD, 8), and 72 mm Hg (SD, 6), respectively. There were significant differences in the jugular venous bulb oxygen tension–brain oxygen tension gradient (16 mm Hg [sd, 6] vs 39 mm Hg SD, 11]; p < 0.001) and in the relationship of jugular venous bulb oxygen tension–brain oxygen tension gradient to cerebral perfusion pressure (p = 0.004) when comparing normoxia to hypoxia. Each 1 mm Hg increase in cerebral perfusion pressure led to a decrease in the jugular venous bulb oxygen tension–brain oxygen tension gradient by 0.36 mm Hg (95% CI, –0.54 to 0.18; p < 0.001) in the normoxia group, but no such relation was demonstrable in the hypoxia group. Conclusions: In hypoxic-ischemic brain injury patients with brain hypoxia, there is an elevation in the jugular venous bulb oxygen tension–brain oxygen tension gradient, which is not modulated by changes in cerebral perfusion pressure. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by grant from the Laerdal Foundation. Dr. Sekhon’s institution received funding from Laerdal Foundation; he received funding from the Clinician Scientist Award from Vancouver Coastal Health Research Institute. Dr. Menon received support for article research from National Institute for Health Research, United Kingdom. Dr. Gooderham received funding from consulting for Stryker Canada and Baxter Canada, and research grants from Brain Aneurysm Foundation and Rare Diseases Foundation (research into Moyamoya disease). Dr. Griesdale is funded through a Health-Professional Investigator Award from the Michael Smith Foundation for Health Research. The remaining authors have disclosed that they do not have any potential conflicts of interest. Trial Registration: NCT03609333—ClinicalTrials.gov. For information regarding this article, E-mail: mypindersekhon@gmail.com Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Evaluation of Serotonin Release Assay and Enzyme-Linked Immunosorbent Assay Optical Density Thresholds for Heparin-Induced Thrombocytopenia in Patients on Extracorporeal Membrane Oxygenation Objectives: Heparin-induced thrombocytopenia is a recognized concern in patients on extracorporeal life support. The purpose of this study was to evaluate the applicability of an enzyme-linked immunosorbent assay optical density threshold less than 1 to rule out heparin-induced thrombocytopenia in patients on extracorporeal membrane oxygenation. Design: Retrospective, single-center study. Setting: Patients were recruited from a prospectively maintained database of all patients on extracorporeal membrane oxygenation from 2012 to 2018 at a tertiary referral center. Patients: Forty-seven patients on extracorporeal membrane oxygenation support. Interventions: The primary objective was to evaluate the application of enzyme-linked immunosorbent assay optical density thresholds and the serotonin release assay in patients on extracorporeal membrane oxygenation. Patients were divided into two cohorts, serotonin release assay negative and serotonin release assay positive. In order to perform a sensitivity and specificity analysis of enzyme-linked immunosorbent assay optical density thresholds, heparin-induced thrombocytopenia negative was defined as an optical density less than 1.0 and heparin-induced thrombocytopenia positive as an optical density greater than or equal to 1.0. Measurements and Main Results: Utilizing the prespecified optical density thresholds, a specificity and negative predictive value of 89% and 95% were achieved, respectively. Conclusions: This assessment has helped to identify optical density thresholds for patients undergoing extracorporeal membrane oxygenation. Our data suggest that an optical density threshold of 1.0 may aid clinicians in objectively ruling out heparin-induced thrombocytopenia without sending a confirmatory serotonin release assay. Increasing the optical density threshold to 1.0 resulted in a high specificity and negative predictive value. Dr. Kataria is the guarantor of the content of the article, including the data and analysis. Drs. Moore, Harrison, Hernandez, Vaughan, and Schwartz served as co-investigators. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Vivek.Kataria@BSWHealth.org Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Systematic Review and Meta-Analysis of Effects of Transfusion on Hemodynamic and Oxygenation Variables Objectives: RBC transfusions can increase oxygen availability to the tissues, but studies have provided conflicting results. The objectives of this study were, therefore, to evaluate, using systematic review and meta-analysis, the effects of transfusion on hemodynamic/oxygenation variables in patients without acute bleeding. Data Sources: PubMed, Scopus, Cochrane Database of Systematic Reviews, and Embase from inception until June 30, 2019. Study Selection: All articles that reported values of prespecified hemodynamic or oxygenation variables before and after RBC transfusion. Data Extraction: Publication year, number of patients, number of transfusions and the type of population studied, hemodynamic and oxygenation data (heart rate, cardiac index, mixed venous oxygen saturation or central venous oxygen saturation, oxygen delivery index, oxygen consumption index, oxygen extraction ratio, arteriovenous oxygen difference and arterial blood lactate) before and after transfusion. We performed a meta-analysis for each variable for which there were sufficient data to estimate mean differences. We also performed subgroup analyses comparing septic with nonseptic patients. Data Synthesis: We retrieved 6,420 studies; 33 met the inclusion criteria, 14 of which were in patients with sepsis. In the meta-analysis, the estimated mean differences and 95% CIs comparing the periods before and after transfusion were –0.0 L/min/m2 (–0.1 to 0.1 L/min/m2) (p = 0.86) for cardiac index; –1.8 beats/min (–3.7 to 0.1 beats/min) (p = 0.06) for heart rate; 96.8 mL/min/m2 (71.1–122.5 mL/min/m2) (p < 0.01) for oxygen delivery index; 2.9% (2.2–3.5%) (p < 0.01) for mixed venous oxygen saturation or central venous oxygen saturation; –3.7% (–4.4% to –3.0%) (p < 0.01) for oxygen extraction ratio; and 4.9 mL/min/m2 (0.9–9.0 mL/min/m2) (p = 0.02) for oxygen consumption index. The estimated mean difference for oxygen consumption index in the patients with sepsis was 8.4 mL/min/m2 (2.3–14.5 mL/min/m2; p = 0.01). Conclusions: Transfusion was not associated with a decrease in mean cardiac output or mean heart rate. The increase in mean oxygen delivery following transfusion was associated with an increase in mean oxygen consumption after transfusion, especially in patients with sepsis. Dr. Cavalcante dos Santos helped design the study, performed the literature review, extracted the data, analyzed data, drafted the article, and read and approved the final version. Dr. Orbegozo helped design the study, performed the literature review, extracted the data, revised the article for intellectual content, and read and approved the final version. Drs. Mongkolpun, Galfo, Nan, and Bogossian performed the literature review, extracted the data, revised the article for intellectual content, and read and approved the final version. Dr. Taccone revised the article for intellectual content, read and approved the final version. Dr. Vallet provided data, revised the article for intellectual content, and read and approved the final version. Dr. Creteur revised the article for intellectual content, read and approved the final version. Dr. Vincent helped design the study, helped interpret the data, revised the article for intellectual content, and read and approved the final version. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: jlvincent@intensive.org Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Comparative Performance of Pulmonary Ultrasound, Chest Radiograph, and CT Among Patients With Acute Respiratory Failure Objectives: The study goal was to concurrently evaluate agreement of a 9-point pulmonary ultrasound protocol and portable chest radiograph with chest CT for localization of pathology to the correct lung and also to specific anatomic lobes among a diverse group of intubated patients with acute respiratory failure. Design: Prospective cohort study. Setting: Medical, surgical, and neurologic ICUs at a 670-bed urban teaching hospital. Patients: Intubated adults with acute respiratory failure having chest CT and portable chest radiograph performed within 24 hours of intubation. Interventions: A 9-point pulmonary ultrasound examination performed at the time of intubation. Measurements and Main Results: Sixty-seven patients had pulmonary ultrasound, portable chest radiograph, and chest CT performed within 24 hours of intubation. Overall agreement of pulmonary ultrasound and portable chest radiograph findings with correlating lobe (“lobe-specific” agreement) on CT was 87% versus 62% (p < 0.001), respectively. Relaxing the agreement definition to a matching CT finding being present anywhere within the correct lung (“lung-specific” agreement), not necessarily the specific mapped lobe, showed improved agreement for both pulmonary ultrasound and portable chest radiograph respectively (right lung: 92.5% vs 65.7%; p < 0.001 and left lung: 83.6% vs 71.6%; p = 0.097). The highest lobe-specific agreement was for the finding of atelectasis/consolidation for both pulmonary ultrasound and portable chest radiograph (96% and 73%, respectively). The lowest lobe-specific agreement for pulmonary ultrasound was normal lung (79%) and interstitial process for portable chest radiograph (29%). Lobe-specific agreement differed most between pulmonary ultrasound and portable chest radiograph for interstitial findings (86% vs 29%, respectively). Pulmonary ultrasound had the lowest agreement with CT for findings in the left lower lobe (82.1%). Pleural effusion agreement also differed between pulmonary ultrasound and portable chest radiograph (right: 99% vs 87%; p = 0.009 and left: 99% vs 85%; p = 0.004). Conclusions: A clinical, 9-point pulmonary ultrasound protocol strongly agreed with specific CT findings when analyzed by both lung- and lobe-specific location among a diverse population of mechanically ventilated patients with acute respiratory failure; in this regard, pulmonary ultrasound significantly outperformed portable chest radiograph. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Tierney received funding from personally purchased stock options and disclosed he is a member of Medical Advisory Boards for Echonous and Bay Labs. The remaining authors have disclosed that they do not have any potential conflicts of interest. This work was performed at Abbott Northwestern Hospital, Minneapolis, MN. For information regarding this article, E-mail: david.tierney@allina.com Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Epinephrine for Out-of-Hospital Cardiac Arrest: An Updated Systematic Review and Meta-Analysis Objectives: To perform an updated systematic review and meta-analysis of clinical trials evaluating epinephrine for adult out-of-hospital cardiac arrest resuscitation. Data Sources: The search included MEDLINE, EMBASE, and Ovid Evidence-Based Medicine, clinical trial registries, and bibliographies. Study Selection: Randomized and quasi-randomized controlled trials that compared the current standard dose of epinephrine to placebo, high or low dose epinephrine, any other vasopressor alone or in combination were screened by three independent reviewers. Data Extraction: Randomized and quasi-randomized controlled trials that compared the current standard dose of epinephrine to placebo, high or low dose epinephrine, any other vasopressor alone or in combination were screened by three independent reviewers. Data Synthesis: A total of 17 trials (21,510 patients) were included; seven were judged to be at high risk of bias. Compared to placebo, pooled results from two trials showed that standard dose of epinephrine increased return of spontaneous circulation (risk ratio, 3.09; 95% CI, 2.82–3.89), survival to hospital admission (risk ratio, 2.50; 95% CI, 1.68–3.72), and survival to discharge (risk ratio, 1.44; 95% CI, 1.11–1.86). The largest placebo-controlled trial showed that standard dose of epinephrine also improved survival at 30 days and 3 months but not neurologic outcomes, standard dose of epinephrine decreased return of spontaneous circulation (risk ratio, 0.87; 95% CI, 0.77–0.98) and survival to admission (risk ratio, 0.88; 95% CI, 0.78–0.99) when compared with high dose epinephrine. There were no differences in outcomes between standard dose of epinephrine and vasopressin alone or in combination with epinephrine. Conclusions: Largely based on one randomized controlled trial, standard dose of epinephrine improved overall survival but not neurologic outcomes in out-of-hospital cardiac arrest patients compared with placebo. There is a paucity of trials with meaningful patient outcomes; future epinephrine trials should evaluate dose and method of delivery on long-term survival, neurologic function, and quality of life after cardiac arrest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Lin is an Investigator of the Cardiac Arrhythmia Network of Canada as part of the Networks of Centres of Excellence and is the Co-Principal Investigator of a Canadian Institutes of Health Research Project Grant for a clinical trial to evaluate low-dose epinephrine during cardiac arrest resuscitation, and he was an Evidence Reviewer for the C2015 International Liaison Committee on Resuscitation advanced life support Taskforce. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: steve.lin@unityhealth.to Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.